Phosphatidylethanolamine synthesis is required for optimal virulence of Brucella abortus.
The Brucella cell envelope contains the zwitterionic phospholipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Synthesis of PC occurs exclusively via the PC synthase pathway, implying that the pathogen depends on the choline synthesized by the host cell to form PC. Notably, PC is necessary to sustain a chronic infection process, which suggests that the membrane lipid content is relevant for Brucella virulence. In this study we investigated the first step of PE biosynthesis in B. abortus, which is catalyzed by phosphatidylserine synthase (PssA). Disruption of pssA abrogated the synthesis of PE without affecting the growth in rich complex medium. In minimal medium, however, the mutant required choline supplementation for growth, suggesting that at least PE or PC is necessary for Brucella viability. The absence of PE altered cell surface properties, but most importantly, it impaired several virulence traits of B. abortus, such as intracellular survival in both macrophages and HeLa cells, the maturation of the replicative Brucella-containing vacuole, and mouse colonization. These results suggest that membrane phospholipid composition is critical for the interaction of B. abortus with the host cell.
Bukata
Lucas
L
Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, CONICET, San Martín, Buenos Aires, Argentina.
Altabe
Silvia
S
de Mendoza
Diego
D
Ugalde
Rodolfo A
RA
Comerci
Diego J
DJ
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002003:Brucella abortus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D002006:Brucellosis / Q000382:microbiology; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D055786:Gene Knockout Techniques; D005798:Genes, Bacterial; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010714:Phosphatidylethanolamines / Q000096:biosynthesis*; D010957:Plasmids; D014774:Virulence
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase